Recent data have shown the following: 1. There is a "factor" extractable from human urine which stimulates NH4 ion excretion in the toad bladder when the subject is in an NH4Cl induced acidosis. 2. This same factor when injected into the renal artery of a dog will also produce an increased excretion of NH4 ion by the kidney while having no effect on H ion excretion (one dog). Paired hemibladders mounted between lucite chambers were used to obtain the data in items 1-2 above. One hemibladder is a control hemibladder and the other hemibladder from the same toad is the experimental hemibladder. Using these methods we are expending the series of experiments on obtaining this factor from the urine of other human subjects and to improve the extraction procedure for obtaining the factor. We are also doing a correlative study on the scanning electron micrograph findings compared with changes in transmission electron micrographs of the toad bladder mucosal cells, while in metabolic acidosis. We propose to determine if the factor is active in the mammalian nephron as well as the toad bladder by infusing it into the renal artery of the dog. In addition, we are carrying out experiments to determine if there is a relationship between H ion and K ion excretion in the toad urinary bladder in response to changes in acid-base state of the toad. Also, it has been shown that the vasopressin stimulated water flow is altered by changes in the acid-base state of the toad. Experiments are being done which will help elucidate the mechanism by which this alteration in vasopressin stimulated water flow is brought about.